SAN ANTONIO — Accelerated partial breast irradiation appears close but not equivalent to whole breast irradiation for control of ipsilateral breast tumor recurrence and risk for recurrence-free interval events, according to results of a randomized phase 3 trial presented at San Antonio Breast Cancer Symposium.

“[However], because the absolute differences relative to both ipsilateral breast tumor recurrence and recurrence-free interval [events] were very small, partial-breast irradiation may be an acceptable alternative to whole breast irradiation for a proportion of women who undergo breast-conserving surgery,” Frank Vicini, MD, principal investigator at MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Michigan, said during a press conference.

In the NSABP B-39/RTOG 0413 trial, Vicini and colleagues aimed to reduce overall treatment time and improve quality of life for patients by evaluating partial breast irradiation (PBI), which limits radiation to the lumpectomy cavity and can be completed in 5 to 10 days.

WBI regimens were 50 Gy (2 Gy per fraction) or 50.4 Gy (1.8 Gy per fraction) followed by an optional boost to 60 Gy or higher.

PBI — administered in 10 treatments given on 5 days over a 5- to 10-day period — consisted of 34 Gy in 3.4-Gy fractions via interstitial brachytherapy or MammoSite balloon catheter, or 38.5 Gy in 3.85-Gy fractions via 3-D conformal external beam.

Ipsilateral breast tumor recurrence — both invasive and DCIS — as first recurrence served as the primary endpoint. Secondary endpoints included distant disease-free interval, recurrence-free interval and OS.

Per the protocol-defined margin, the 90% CI for the observed HR had to lie between 0.667 and 1.5 in order for investigators to declare PBI and WBI equivalent with regard to ipsilateral breast tumor recurrence risk.

Researchers observed 161 ipsilateral breast tumor recurrences as first events. These included 90 in the PBI group and 71 in the WBI group (HR = 1.22; 90% CI, 0.94-1.58).

Based on the upper limit of the HR confidence interval, PBI did not meet criterial for equivalence to WBI for this endpoint. However, the absolute difference in 10-year cumulative incidence of ipsilateral breast tumor recurrence between PBI and WBI was only 0.7 percentage points (4.6% vs. 3.9%).

Analysis of recurrence-free interval — defined as time from randomization to development of first local, regional or distant recurrence, regardless of contralateral or second breast cancer — revealed a statistically significant difference between PBI and WBI (10-year rate, 91.8% vs. 93.4%; HR = 1.33; 95% CI, 1.04-1.69).

Additional analyses are underway to assess whether certain subgroups of patients may demonstrate an advantage with regard to local or regional relapse with one of these treatment approaches.

Vicini said his institution continues to offer partial breast irradiation to patients — particularly those who are elderly or who have transportation challenges — within the context of American Society for Radiation Oncology guidelines.

He also emphasized that results must be considered with the context that this trial began 15 years ago and radiation methods have been refined considerably since then.

“This is the largest trial to ever look at partial-breast irradiation within a diverse group of patients,” Vicini said. “Even though we were not able to demonstrate equivalence, it’s nice to see that, in this large population in an extended trial, the differences are quite small,” Vicini said. “At the end of the day, [OS and DFS} are the most important endpoints, but a recurrence is still an important event for patients and our goal is always to limit that as much as possible.”

At the same time, there are dramatic differences between these two treatment approaches that result in greatly improved quality of life for patients who undergo PBI.

“If there is a 0.7% higher risk for recurrence, how does that get offset when you know the survival rates are the same?” Vicini said. “That is what patients and doctors need to take into consideration.” – by Mark Leiser

Vicini reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.

SAN ANTONIO — Accelerated partial breast irradiation appears close but not equivalent to whole breast irradiation for control of ipsilateral breast tumor recurrence and risk for recurrence-free interval events, according to results of a randomized phase 3 trial presented at San Antonio Breast Cancer Symposium.

“[However], because the absolute differences relative to both ipsilateral breast tumor recurrence and recurrence-free interval [events] were very small, partial-breast irradiation may be an acceptable alternative to whole breast irradiation for a proportion of women who undergo breast-conserving surgery,” Frank Vicini, MD, principal investigator at MHP Radiation Oncology Institute/21st Century Oncology in Pontiac, Michigan, said during a press conference.

In the NSABP B-39/RTOG 0413 trial, Vicini and colleagues aimed to reduce overall treatment time and improve quality of life for patients by evaluating partial breast irradiation (PBI), which limits radiation to the lumpectomy cavity and can be completed in 5 to 10 days.

WBI regimens were 50 Gy (2 Gy per fraction) or 50.4 Gy (1.8 Gy per fraction) followed by an optional boost to 60 Gy or higher.

PBI — administered in 10 treatments given on 5 days over a 5- to 10-day period — consisted of 34 Gy in 3.4-Gy fractions via interstitial brachytherapy or MammoSite balloon catheter, or 38.5 Gy in 3.85-Gy fractions via 3-D conformal external beam.

Ipsilateral breast tumor recurrence — both invasive and DCIS — as first recurrence served as the primary endpoint. Secondary endpoints included distant disease-free interval, recurrence-free interval and OS.

Per the protocol-defined margin, the 90% CI for the observed HR had to lie between 0.667 and 1.5 in order for investigators to declare PBI and WBI equivalent with regard to ipsilateral breast tumor recurrence risk.

Researchers observed 161 ipsilateral breast tumor recurrences as first events. These included 90 in the PBI group and 71 in the WBI group (HR = 1.22; 90% CI, 0.94-1.58).

Based on the upper limit of the HR confidence interval, PBI did not meet criterial for equivalence to WBI for this endpoint. However, the absolute difference in 10-year cumulative incidence of ipsilateral breast tumor recurrence between PBI and WBI was only 0.7 percentage points (4.6% vs. 3.9%).

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Analysis of recurrence-free interval — defined as time from randomization to development of first local, regional or distant recurrence, regardless of contralateral or second breast cancer — revealed a statistically significant difference between PBI and WBI (10-year rate, 91.8% vs. 93.4%; HR = 1.33; 95% CI, 1.04-1.69).

Additional analyses are underway to assess whether certain subgroups of patients may demonstrate an advantage with regard to local or regional relapse with one of these treatment approaches.

Vicini said his institution continues to offer partial breast irradiation to patients — particularly those who are elderly or who have transportation challenges — within the context of American Society for Radiation Oncology guidelines.

He also emphasized that results must be considered with the context that this trial began 15 years ago and radiation methods have been refined considerably since then.

“This is the largest trial to ever look at partial-breast irradiation within a diverse group of patients,” Vicini said. “Even though we were not able to demonstrate equivalence, it’s nice to see that, in this large population in an extended trial, the differences are quite small,” Vicini said. “At the end of the day, [OS and DFS} are the most important endpoints, but a recurrence is still an important event for patients and our goal is always to limit that as much as possible.”

At the same time, there are dramatic differences between these two treatment approaches that result in greatly improved quality of life for patients who undergo PBI.

“If there is a 0.7% higher risk for recurrence, how does that get offset when you know the survival rates are the same?” Vicini said. “That is what patients and doctors need to take into consideration.” – by Mark Leiser

Vicini reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.

Perspective

The successful completion and reporting of the B39 trial is a huge testament to the significance of this topic in the radiation oncology community.

Our general impression is that PBI remains a safe alternative for women with favorable-risk, early-stage breast cancer who cannot or choose not to receive WBI. Although the difference between PBI and WBI was not statistically significant in terms of clinical endpoints such as ipsilateral breast tumor recurrence, distant disease-free interval or OS, the use of PBI resulted in a lower recurrence-free interval at 10 years compared with WBI. However, whether this small absolute difference in recurrence-free interval translates into clinically meaningful differences is debatable. This data must be acknowledged in context ofmodestly higher grade 3 or higher toxicities with PBI.

The results are not surprising, as we would not necessarily assume inferiority of PBI in terms oflocal control or survival outcomes, which are already excellent in the era of effective systemic therapy for women with early-stage breast cancer. Patients and clinicians can be comforted by the results of B39, but we still await data regarding the long-term effects on cosmesis and quality of life with PBI, and how these noncancer outcomes are impacted by differences in radiation dose, technique, fractionation and quality, all of which seems to vary depending on institution and individual clinicians. Future reporting of subgroups of patients who may benefit from PBI will further enrich our interpretation of this landmark study.

Alice Ho, MD, and Alphonse Taghian, MD

Massachusetts General Hospital

Disclosures: Ho reports consultant roles with Amgen and Merck, as well as research funding from Merck and Tesaro. Taghian reports no relevant financial disclosures.